chr17-80415704-G-C

Position:

• chr17-80415704-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173627.5(ENDOV):​c.111G>C​(p.Gln37His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,826 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ENDOV NM_173627.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

Genes affected

ENDOV (HGNC:26640): (endonuclease V) Enables DNA binding activity; endoribonuclease activity, producing 5'-phosphomonoesters; and single-stranded RNA binding activity. Predicted to be involved in DNA repair. Located in cytoplasmic stress granule and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENDOV	NM_173627.5	c.111G>C	p.Gln37His	missense_variant	2/10	ENST00000518137.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENDOV	ENST00000518137.6	c.111G>C	p.Gln37His	missense_variant	2/10	2	NM_173627.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458826 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725438

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.111G>C (p.Q37H) alteration is located in exon 2 (coding exon 2) of the ENDOV gene. This alteration results from a G to C substitution at nucleotide position 111, causing the glutamine (Q) at amino acid position 37 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T;.
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.62	D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.9	M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;N;N;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.21
Sift	Benign	0.069	T;T;T;T
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.61
MutPred		0.36		Loss of MoRF binding (P = 0.1512);Loss of MoRF binding (P = 0.1512);Loss of MoRF binding (P = 0.1512);Loss of MoRF binding (P = 0.1512);
MVP		0.64
MPC		0.083
ClinPred		0.99	D
GERP RS		0.34
Varity_R		0.78
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2081027458; hg19: chr17-78389504;